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Androgen Deficiency and Testosterone Replacement pp 55–72Cite as

Testosterone and Its Association with Metabolic and Cardiovascular Disease

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Part of the book series: Current Clinical Urology ((CCU))

Abstract

Epidemiological evidence documents that women outlive men, and the exact reasons for this higher gender-specific mortality are not fully understood. Data from the last few decades suggest that low serum testosterone (T) is associated with increased male morbidity and mortality. Subjects with obesity, type 2 diabetes mellitus (T2DM), metabolic syndrome (MetS), and cardiovascular disease (CVD) often have reduced levels of T in comparison to healthy subjects. Experimental data indicate that T exerts a protective effect on vascular function; however, the relationship between CVD and serum T levels in men remains contradictory. Two recent meta-analyses have shown that low endogenous T levels are associated with an increased risk of all-cause and CVD death, but not with incident CVD. In addition, three meta-analyses found no significant effect of T replacement therapy on the occurrence of CV events. Hence, the main issue regarding the association between male hypogonadism and CVD is that it is not apparent which one is the cause and which is the consequence.

In prostate cancer patients, the increased prevalence of obesity, T2DM, MetS, and CVD, induced by androgen ablation, suggests that T suppression is causative. However, the T suppressing effect caused by various chronic diseases (including MetS and T2DM) suggests the opposite. Therefore, while low T may contribute to the pathogenesis of CVD, the reverse is also possible. One cannot exclude the possibility that low T, as observed in several chronic diseases, represents an adaptive mechanism for turning off T-dependent functions (such as reproduction and physical vigor) that are not needed when the organism is sick.

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References

  1. National Center for Health Statistics. Health, United States, 2006: with chartbook on trends in the health of Americans. Hyattsville: National Center for Health Statistics (US); 2006.

    Google Scholar 

  2. Johnson FW, Gruenewald PJ, Treno AJ, et al. Drinking over the life course within gender and ethnic groups: a hyperparametric approach. J Stud Alcohol. 1998;59:568–81.

    CAS  PubMed  Google Scholar 

  3. York JL, Welte J, Hirsch J. Gender composition of alcohol exposure on drinking occasions. J Stud Alcohol. 2003;64:790–801.

    PubMed  Google Scholar 

  4. Miniño AM, Heron MP, Murphy SL, Kochanek KD. Centers for Disease Control and Prevention National Center for Health Statistics National Vital Statistics System. Deaths: final data for 2004. Natl Vital Stat Rep. 2007 Aug 21;55(19):1–119.

    Google Scholar 

  5. Barbeau EM, Krieger N, Soobader MJ. Working class matters: socioeconomic disadvantage, race/ethnicity, gender, and smoking in NHIS 2000. Am J Public Health. 2004;94:269–78.

    Article  PubMed  Google Scholar 

  6. Wallace Jr JM, Bachman JG, O’Malley PM, et al. Gender and ethnic differences in smoking, drinking and illicit drug use among American 8th, 10th, and 12th grade students, 1976–2000. Addiction. 2003;98:225–34.

    Article  PubMed  Google Scholar 

  7. Corona G, Rastrelli G, Vignozzi L, et al. Testosterone, cardiovascular disease and the metabolic syndrome. Best Pract Res Clin Endocrinol Metab. 2011;25:337–53.

    Article  CAS  PubMed  Google Scholar 

  8. Wu FC, von Eckardstein A. Androgens and coronary artery disease. Endocr Rev. 2003;24:183–217.

    Article  CAS  PubMed  Google Scholar 

  9. Corona G, Mannucci E, Forti G, et al. Hypogonadism, ED, metabolic syndrome and obesity: a pathological link supporting cardiovascular diseases. Int J Androl. 2009;32:587–98.

    Article  CAS  PubMed  Google Scholar 

  10. Corona G, Mannucci E, Fisher AD, et al. Low levels of androgens in men with erectile dysfunction and obesity. J Sex Med. 2008;5:2454–63.

    CAS  PubMed  Google Scholar 

  11. Saad F, Aversa A, Isidori AM, et al. Testosterone as potential effective therapy in treatment of obesity in men with testosterone deficiency: a review. Curr Diabetes Rev. 2012;23:8.

    Google Scholar 

  12. Traish AM, Guay A, Feeley R, et al. The dark side of testosterone deficiency: I. Metabolic syndrome and erectile dysfunction. J Androl. 2009;30:10–22.

    Article  CAS  PubMed  Google Scholar 

  13. Giagulli VA, Kaufman JM, Vermeulen A. Pathogenesis of the decreased androgen levels in obese men. J Clin Endocrinol Metab. 1994;79:997–1000.

    Article  CAS  PubMed  Google Scholar 

  14. Vermeulen A, Kaufman JM, Deslypere JP, et al. Attenuated luteinizing hormone (LH) pulse amplitude but normal LH pulse frequency, and its relation to plasma androgens in hypogonadism of obese men. J Clin Endocrinol Metab. 1993;76:1140–6.

    Article  CAS  PubMed  Google Scholar 

  15. Traish AM, Saad F, Guay A. The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance. J Androl. 2009;30:23–32.

    Article  CAS  PubMed  Google Scholar 

  16. Corona G, Monami M, Rastrelli G, et al. Type 2 diabetes mellitus and testosterone: a meta-analysis study. Int J Androl. 2011;34:528–40.

    Article  CAS  PubMed  Google Scholar 

  17. Wang C, Jackson G, Jones TH, et al. Low testosterone associated with obesity and the metabolic syndrome contributes to sexual dysfunction and cardiovascular disease risk in men with type 2 diabetes. Diabetes Care. 2011;34:1669–75.

    Article  CAS  PubMed  Google Scholar 

  18. Ding EL, Song Y, Malik VS, et al. Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA. 2006;295:1288–99.

    Article  CAS  PubMed  Google Scholar 

  19. Corona G, Mannucci E, Forti G, et al. Following the common association between testosterone deficiency and diabetes mellitus, can testosterone be regarded as a new therapy for diabetes? Int J Androl. 2009;32:431–41.

    Article  CAS  PubMed  Google Scholar 

  20. Anderson SG, Heald A, Younger N, et al. Screening for hypogonadism in diabetes 2008/9: results from the Cheshire Primary Care cohort. Prim Care Diabetes. 2012;6:143–8.

    Article  PubMed  Google Scholar 

  21. Wang C, Nieschlag E, Swerdloff R, et al. Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations. Eur J Endocrinol. 2008;159:507–14.

    Article  CAS  PubMed  Google Scholar 

  22. Buvat J, Maggi M, Gooren L, et al. Endocrine aspects of male sexual dysfunctions. In: Montorsi F, Basson R, Adaikan G, Becher E, Clayton A, Giuliano G, Khoury S, Sharlip I, editors. Sexual medicine, sexual dysfunctions in men and women. Proceedings of the 3rd international consultation on sexual medicine. Paris: Health Publication Ltd; 2010. p. 681.

    Google Scholar 

  23. Dhindsa S, Prabhakar S, Sethi M, et al. Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes. J Clin Endocrinol Metab. 2004;89:5462–8.

    Article  CAS  PubMed  Google Scholar 

  24. Kumai T, Tanaka M, Watanabe M, et al. Possible involvement of androgen in increased norepinephrine synthesis in blood vessels of spontaneously hypertensive rats. Jpn J Pharmacol. 1994;66:439–44.

    Article  CAS  PubMed  Google Scholar 

  25. Cambotti LJ, Cole FE, Gerall AA, et al. Neonatal gonadal hormones and blood pressure in the spontaneously hypertensive rat. Am J Physiol. 1984;247:E258–64.

    CAS  PubMed  Google Scholar 

  26. Reckelhoff JF, Zhang H, Granger JP. Testosterone exacerbates hypertension and reduces pressure-natriuresis in male spontaneously hypertensive rats. Hypertension. 1998;31:435–9.

    Article  CAS  PubMed  Google Scholar 

  27. Yanes LL, Iliescu R, Sartori-Valinotti JC, et al. Testosteronedependent hypertension and upregulation of intrarenal angiotensinogen in Dahl salt-sensitive rats. Am J Physiol Renal Physiol. 2009;296:F771–9.

    Article  CAS  PubMed  Google Scholar 

  28. Hughes GS, Mathur RS, Margolius HS. Sex steroid hormones are altered in essential hypertension. J Hypertens. 1989;7:181–7.

    Article  CAS  PubMed  Google Scholar 

  29. Svartberg J, von Mühlen D, Schirmer H, et al. Association of endogenous testosterone with blood pressure and left ventricular mass in men. The Tromsø Study. Eur J Endocrinol. 2004;150:65–71.

    Article  CAS  PubMed  Google Scholar 

  30. Labropoulos B, Velonakis E, Oekonomakos P, et al. Serum sex hormones in patients with coronary disease and their relationship to known factors causing atherosclerosis. Cardiology. 1982;69:98–103.

    Article  CAS  PubMed  Google Scholar 

  31. Corona G, Rastrelli G, Morelli A, et al. Hypogonadism and metabolic syndrome. J Endocrinol Invest. 2011;34:557–67.

    CAS  PubMed  Google Scholar 

  32. Corona G, Mannucci E, Lotti F, et al. Pulse pressure, an index of arterial stiffness, is associated with androgen deficiency and impaired penile blood flow in men with ED. J Sex Med. 2009;6:285–93.

    Article  CAS  PubMed  Google Scholar 

  33. Fogari R, Preti P, Zoppi A, et al. Serum testosterone levels and arterial blood pressure in the elderly. Hypertens Res. 2005;28:625–30.

    Article  CAS  PubMed  Google Scholar 

  34. Haffner SM, Mykkanen L, Valdez RA, et al. Relationship of sex hormones to lipids and lipoproteins in nondiabetic men. The Journal of clinical endocrinology and metabolism. 1993;77:1610–5.

    Article  CAS  PubMed  Google Scholar 

  35. Malkin CJ, Pugh PJ, Jones RD, et al. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. The Journal of clinical endocrinology and metabolism. 2004;89:3313–8.

    Article  CAS  PubMed  Google Scholar 

  36. Braga-Basaria M, Muller DC, Carducci MA, et al. Lipoprotein profile in men with prostate cancer undergoing androgen deprivation therapy. International journal of impotence research. 2006;18:494–8.

    Article  CAS  PubMed  Google Scholar 

  37. Smith MR, Finkelstein JS, McGovern FJ, et al. Changes in body composition during androgen deprivation therapy for prostate cancer. The Journal of clinical endocrinology and metabolism. 2002;87:599–603.

    Article  CAS  PubMed  Google Scholar 

  38. Yannucci J, Manola J, Garnick MB, et al. The effect of androgen deprivation therapy on fasting serum lipid and glucose parameters. The Journal of urology. 2006;176:520–5.

    Article  CAS  PubMed  Google Scholar 

  39. Dockery F, Bulpitt CJ, Agarwal S, et al. Testosterone suppression in men with prostate cancer leads to an increase in arterial stiffness and hyperinsulinaemia. Clin Sci (Lond). 2003;104:195–201.

    Article  CAS  PubMed  Google Scholar 

  40. Moorjani S, Dupont A, Labrie F, et al. Changes in plasma lipoproteins during various androgen suppression therapies in men with prostatic carcinoma: effects of orchiectomy, estrogen, and combination treatment with luteinizing hormone-releasing hormone agonist and flutamide. The Journal of clinical endocrinology and metabolism. 1988;66:314–22.

    Article  CAS  PubMed  Google Scholar 

  41. Smith JC, Bennett S, Evans LM, et al. The effects of induced hypogonadism on arterial stiffness, body composition, and metabolic parameters in males with prostate cancer. The Journal of clinical endocrinology and metabolism. 2001;86:4261–7.

    Article  CAS  PubMed  Google Scholar 

  42. Corona G, Monami M, Rastrelli G, et al. Testosterone and metabolic syndrome: a meta-analysis study. J Sex Med. 2011;8:272–83.

    Article  CAS  PubMed  Google Scholar 

  43. Brand JS, van der Tweel I, Grobbee DE, et al. Testosterone, sex hormone-binding globulin and the metabolic syndrome: a systematic review and meta-analysis of observational studies. Int J Epidemiol. 2011;40:189–207.

    Article  PubMed  Google Scholar 

  44. Wu FC, Tajar A, Beynon JM, et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med. 2010;363:123–35.

    Article  CAS  PubMed  Google Scholar 

  45. Singh R, Artaza JN, Taylor WE, et al. Testosterone inhibits adipogenic differentiation in 3T3-L1 cells: nuclear translocation of androgen receptor complex with beta-catenin and T-cell factor 4 may bypass canonical Wnt signaling to down-regulate adipogenic transcription factors. Endocrinology. 2006;147:141–54.

    Article  CAS  PubMed  Google Scholar 

  46. Corona G, Rastrelli G, Monami M, et al. Hypogonadism as a risk factor for cardiovascular mortality in men: a meta-analytic study. Eur J Endocrinol. 2011;165:687–701.

    Article  CAS  PubMed  Google Scholar 

  47. Marin P, Oden B, Bjorntorp P. Assimilation and mobilization of triglycerides in subcutaneous abdominal and femoral adipose tissue in vivo in men: effects of androgens. J Clin Endocrinol Metab. 1995;80:239–43.

    Article  CAS  PubMed  Google Scholar 

  48. Corona G, Forti G, Maggi M. Why can patients with erectile dysfunction be considered lucky? The association with testosterone deficiency and metabolic syndrome. Aging Male. 2008;11:193–9.

    Article  CAS  PubMed  Google Scholar 

  49. Zhang XH, Filippi S, Morelli A, et al. Testosterone restores diabetes-induced erectile dysfunction and sildenafil responsiveness in two distinct animal models of chemical diabetes. J Sex Med. 2006;3:253–64.

    Article  CAS  PubMed  Google Scholar 

  50. Vignozzi L, Morelli A, Filippi S, et al. Testosterone regulates RhoA/Rho-kinase signaling in two distinct animal models of chemical diabetes. J Sex Med. 2007;4:620–30.

    Article  CAS  PubMed  Google Scholar 

  51. Brüning JC, Gautam D, Burks DJ, et al. Role of brain insulin receptor in control of body weight and reproduction. Science. 2007;289:2122–5.

    Article  Google Scholar 

  52. Corona G, Mannucci E, Petrone L, et al. Association of hypogonadism and type II diabetes in men attending an outpatient erectile dysfunction clinic. Int J Impot Res. 2006;18:190–7.

    Article  CAS  PubMed  Google Scholar 

  53. Corona G, Mannucci E, Schulman C, et al. Psychobiologic correlates of the metabolic syndrome and associated sexual dysfunction. Eur Urol. 2006;50:595–604.

    Article  PubMed  Google Scholar 

  54. Loves S, Ruinemans-Koerts J, de Boer H. Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism. Eur J Endocrinol. 2008;158:741–7.

    Article  CAS  PubMed  Google Scholar 

  55. Pitteloud N, Hardin M, Dwyer AA, et al. Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men. J Clin Endocrinol Metab. 2005;90:2636–41.

    Article  CAS  PubMed  Google Scholar 

  56. Pitteloud N, Dwyer AA, DeCruz S, et al. Inhibition of LH secretion by testosterone in men requires aromatization for its pituitary but not its hypothalamic effects: evidence from the tandem study of normal and gonadotrophin-releasing hormone-deficient men. J Clin Endocrinol Metab. 2008;93:784–91.

    Article  CAS  PubMed  Google Scholar 

  57. Pasquali R, Casimirri F, De Iasio R, et al. Insulin regulates testosterone and sex hormone-binding globulin concentrations in adult normal weight and obese men. J Clin Endocrinol Metab. 1995;80:654–8.

    Article  CAS  PubMed  Google Scholar 

  58. Isidori AM, Caprio M, Strollo F, et al. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. J Clin Endocrinol Metab. 1999;84:3673–80.

    Article  CAS  PubMed  Google Scholar 

  59. Isidori AM, Strollo F, Morè M, et al. Leptin and aging: correlation with endocrine changes in male and female healthy adult populations of different body weights. J Clin Endocrinol Metab. 2000;85:1954–62.

    Article  CAS  PubMed  Google Scholar 

  60. Morales V, Santana P, Díaz R, et al. Intratesticular delivery of tumor necrosis factor-alpha and ceramide directly abrogates steroidogenic acute regulatory protein expression and Leydig cell steroidogenesis in adult rats. Endocrinology. 2003;144:4763–72.

    Article  CAS  PubMed  Google Scholar 

  61. McEwan DJ. Interactions between TNF and GnRH. Neurochem Res. 2008;33:678–82.

    Article  CAS  Google Scholar 

  62. Araujo AB, Dixon JM, Suarez EA, et al. Clinical review: endogenous testosterone and mortality in men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2011;96:3007–19.

    Article  CAS  PubMed  Google Scholar 

  63. Keating NL, O’Malley AJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol. 2006;24:4448–56.

    Article  CAS  PubMed  Google Scholar 

  64. Saigal CS, Gore JL, Krupski TL, et al. Androgen deprivation therapy increases cardiovascular morbidity in men with prostate cancer. Cancer. 2007;110:1493–500.

    Article  CAS  PubMed  Google Scholar 

  65. D’Amico AV, Denham JW, Crook J, et al. Influence of androgen suppression therapy for prostate cancer on the frequency and timing of fatal myocardial infarctions. J Clin Oncol. 2007;25:2420–5.

    Article  PubMed  CAS  Google Scholar 

  66. Tsai HK, D’Amico AV, Sadetsky N, et al. Androgen deprivation therapy for localized prostate cancer and the risk of cardiovascular mortality. J Natl Cancer Inst. 2007;99:1516–24.

    Article  PubMed  Google Scholar 

  67. Efstathiou JA, Bae K, Shipley WU, et al. Cardiovascular mortality and duration of androgen deprivation for locally advanced prostate cancer: analysis of RTOG 92–02. Eur Urol. 2008;54:816–23.

    Article  CAS  PubMed  Google Scholar 

  68. Efstathiou JA, Bae K, Shipley WU, et al. Cardiovascular mortality after androgen deprivation therapy for locally advanced prostate cancer: RTOG 85–31. J Clin Oncol. 2009;27:92–9.

    Article  PubMed  Google Scholar 

  69. Roach 3rd M, Bae K, Speight J, et al. Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610. J Clin Oncol. 2008;26:585–91.

    Article  PubMed  Google Scholar 

  70. Bolla M, de Reijke TM, Van Tienhoven G, et al. Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med. 2009;360:2516–27.

    Article  CAS  PubMed  Google Scholar 

  71. Corona G, Monami M, Boddi V, et al. Low testosterone is associated with an increased risk of MACE lethality in subjects with erectile dysfunction. J Sex Med. 2010;7:1557–64.

    Article  CAS  PubMed  Google Scholar 

  72. Tomlinson JW, Holden N, Hills RK, et al. Association between premature mortality and hypopituitarism. West Midlands Prospective Hypopituitary Study Group. Lancet. 2001;357:425–31.

    Article  CAS  PubMed  Google Scholar 

  73. Bojesen A, Juul S, Birkebaek N, et al. Increased mortality in Klinefelter syndrome. J Clin Endocrinol Metab. 2004;89:3830–4.

    Article  CAS  PubMed  Google Scholar 

  74. Hamilton JB, Mestler GE. Mortality and survival: comparison of eunuchs with intact men and women in a mentally retarded population. J Gerontol. 1969;24:395–411.

    Article  CAS  PubMed  Google Scholar 

  75. Shores MM, Matsumoto AM, Sloan KL, et al. Low serum testosterone and mortality in male veterans. Arch Intern Med. 2006;166:1660–5.

    Article  CAS  PubMed  Google Scholar 

  76. Akishita M, Hashimoto M, Ohike Y, et al. Low testosterone level as a predictor of cardiovascular events in Japanese men with coronary risk factors. Atherosclerosis. 2010;210:232–6.

    Article  CAS  PubMed  Google Scholar 

  77. Barrett-Connor E, Khaw KT. Endogenous sex hormones and cardiovascular disease in men. A prospective population-based study. Circulation. 1988;78:539–45.

    Article  CAS  PubMed  Google Scholar 

  78. Contoreggi CS, Blackman MR, Andres R, et al. Plasma levels of estradiol, testosterone, and DHEAS do not predict risk of coronary artery disease in men. J Androl. 1990;11:460–70.

    CAS  PubMed  Google Scholar 

  79. Yarnell JW, Beswick AD, Sweetnam PM, et al. Endogenous sex hormones and ischemic heart disease in men. The Caerphilly prospective study. Arterioscler Thromb Vasc Biol. 1993;13:517–20.

    Article  CAS  Google Scholar 

  80. Smith GD, Ben-Shlomo Y, Beswick A, et al. Cortisol, testosterone, and coronary heart disease: prospective evidence from the Caerphilly Study. Circulation. 2005;112:332–40.

    Article  CAS  PubMed  Google Scholar 

  81. Ärnlöv J, Pencina MJ, Amin S, et al. Endogenous sex hormones and cardiovascular disease incidence in men. Ann Intern Med. 2006;145:176–84.

    PubMed  Google Scholar 

  82. Abbott RD, Launer BL, Rodriguez GW, et al. Serum estradiol and risk of stroke in elderly men. Neurology. 2007;68:563–8.

    Article  CAS  PubMed  Google Scholar 

  83. Araujo AB, Kupelian V, Page ST, et al. Sex steroids and all-cause and cause-specific mortality in men. Arch Intern Med. 2007;167:1252–60.

    Article  CAS  PubMed  Google Scholar 

  84. Khaw KT, Dowsett M, Folkerd E, et al. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) prospective population study. Circulation. 2007;116:2694–701.

    Article  CAS  PubMed  Google Scholar 

  85. Maggio M, Lauretani F, Ceda GP, et al. Relationship between low levels of anabolic hormones and 6-year mortality in older men: the Aging in the Chianti Area (INCHIANTI) study. Arch Intern Med. 2007;167:2249–54.

    Article  CAS  PubMed  Google Scholar 

  86. Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab. 2008;93:68–75.

    Article  CAS  PubMed  Google Scholar 

  87. Lehtonen A, Huupponen R, Tuomilehto J, et al. Serum testosterone but not leptin predicts mortality in elderly men. Age Ageing. 2008;37:461–4.

    Article  PubMed  Google Scholar 

  88. Szulc P, Claustrat B, Delmas PD. Serum concentrations of 17β-E2 and 25 hydroxycholecalciferol (25OHD) in relation to all cause mortality in older men—the MINOS study. Clin Endocrinol (Oxf). 2009;71:594–602.

    Article  CAS  Google Scholar 

  89. Tivesten A, Vandenput L, Labrie F, et al. Low serum testosterone and estradiol predict mortality in elderly men. J Clin Endocrinol Metab. 2009;94:2482–8.

    Article  CAS  PubMed  Google Scholar 

  90. Vikan T, Schirmer H, Njølstad I, et al. Endogenous sex hormones and the prospective association with cardiovascular disease and mortality in men: the Tromsø Study. Eur J Endocrinol. 2009;161:435–42.

    Article  CAS  PubMed  Google Scholar 

  91. Yeap BB, Hyde Z, Almeida OP, et al. Lower testosterone levels predict incident stroke and transient ischemic attack in older men. Clin Endocrinol Metab. 2009;94:2353–9.

    Article  CAS  Google Scholar 

  92. Haring R, Völzke H, Steveling A, et al. Low serum testosterone levels are associated with increased risk of mortality in a population-based cohort of men aged 20–79. Eur Heart J. 2010;31:1494–501.

    Article  CAS  PubMed  Google Scholar 

  93. Menke A, Guallar E, Rohrmann S, et al. Sex steroid hormone concentrations and risk of death in US men. Am J Epidemiol. 2010;171:583–92.

    Article  PubMed  Google Scholar 

  94. Hyde Z, Norman PE, Flicker L, et al. Low free testosterone predicts mortality from cardiovascular disease but not other causes: the health in men study. J Clin Endocrinol Metab. 2012;97:179–89.

    Article  CAS  PubMed  Google Scholar 

  95. Corona G, Rastrelli G, Balercia G, Sforza A, Forti G, Maggi M.Testosterone and cardiovascular risk in patients with erectile dysfunction. J Endocrinol Invest. 2011 Nov 8. [Epub ahead of print].

    Google Scholar 

  96. Corona G, Rastrelli G, Monami M, et al. Body mass index regulates hypogonadism-associated CV risk: results from a cohort of subjects with erectile dysfunction. J Sex Med. 2011;8:2098–105.

    Article  PubMed  Google Scholar 

  97. Iervasi G, Pingitore A, Landi P, et al. Low-T3 syndrome: a strong prognostic predictor of death in patients with heart disease. Circulation. 2003;107:708–13.

    Article  PubMed  Google Scholar 

  98. Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363:109–22.

    Article  CAS  PubMed  Google Scholar 

  99. Jones TH. Testosterone deficiency: a risk factor for cardiovascular disease? Trends Endocrinol Metab. 2010;21:496–503.

    Article  CAS  PubMed  Google Scholar 

  100. Malkin CJ, Pugh PJ, Morris PD, et al. Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life. Heart. 2004;90:871–6.

    Article  CAS  PubMed  Google Scholar 

  101. webb CM, Adamson DL, de Zeigler D, et al. Effect of acute testosterone on myocardial ischemia in men with coronary artery disease. Am J Cardiol. 1999;83:437–9.

    Article  CAS  PubMed  Google Scholar 

  102. Foresta C, Caretta N, Lana A, et al. Reduced number of circulating endothelial progenitor cells in hypogonadal men. J Clin Endocrinol Metab. 2006;91:4599–602.

    Article  CAS  PubMed  Google Scholar 

  103. Foresta C, Di Mambro A, Caretta N, et al. Effect of vardenafil on endothelial progenitor cells in hypogonadotrophic hypogonadal patients: role of testosterone treatment. Clin Endocrinol. 2008;71:412–6.

    Article  CAS  Google Scholar 

  104. Jin H, Lin J, Fu L, et al. Physiological testosterone stimulates tissue plasminogen activator and tissue factor pathway inhibitor and inhibits plasminogen activator inhibitor type 1 release in endothelial cells. Biochem Cell Biol. 2007;85:246–51.

    Article  CAS  PubMed  Google Scholar 

  105. Isidori AM, Giannetta E, Greco EA, et al. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol (Oxf). 2005;63:280–93.

    Article  CAS  Google Scholar 

  106. Whitsel EA, Boyko EJ, Matsumoto AM, et al. Intramuscular testosterone esters and plasma lipids in hypogonadal men: a meta-analysis. Am J Med. 2001;111:261–9.

    Article  CAS  PubMed  Google Scholar 

  107. Haddad RM, Kennedy CC, Caples SM, et al. Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin Proc. 2007;82:29–39.

    CAS  PubMed  Google Scholar 

  108. Fernández-Balsells MM, Murad MH, Lane M, et al. Clinical review 1: adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2010;95:2560–75.

    Article  PubMed  CAS  Google Scholar 

  109. Calof OM, Singh AB, Lee ML, et al. Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol A Biol Sci Med Sci. 2005;60:1451–7.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Andrology and Sexual Medicine Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy

    Giovanni Corona MD, PhD, Giulia Rastrelli MD & Mario Maggi MD

  2. Endocrinology Unit, Maggiore-Bellaria Hospital, Bologna, Italy

    Giovanni Corona MD, PhD

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  1. Giovanni Corona MD, PhD
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  2. Giulia Rastrelli MD
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Correspondence to Mario Maggi MD .

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  1. , Department of Urology, Tulane University Medical Center, 1430 Tulane Ave. SL-42, New Orleans, 70112, Louisiana, USA

    Wayne J.G. Hellstrom

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Corona, G., Rastrelli, G., Maggi, M. (2013). Testosterone and Its Association with Metabolic and Cardiovascular Disease. In: Hellstrom, W. (eds) Androgen Deficiency and Testosterone Replacement. Current Clinical Urology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-179-0_5

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  • DOI: https://doi.org/10.1007/978-1-62703-179-0_5

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